biostudies-literatureUnknown6(2)Syamprasad NP<h4>Background & aims</h4>The mechanism behind the progressive pathological alteration in metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH)-associated hepatocellular carcinoma (HCC) is poorly understood. In the present study, we investigated the role of the polyol pathway enzyme AKR1B1 in metabolic switching associated with MASLD/MASH and in the progression of HCC.<h4>Methods</h4>AKR1B1 expression was estimated in the tissue and plasma of patients with MASLD/MASH, HCC, and HCC with diabetes mellitus. The role of AKR1B1 in metabolic switching <i>in vitro was</i> assessed through media conditioning, lentiviral transfection, and pharmacological probes. A proteomic and metabolomic approach was applied for the in-depth investigation of metabolic pathways. PreJHEP reports : innovation in hepatology100974https://www.ebi.ac.uk/biostudies/studies/S-EPMC10820337biostudies-literatureAKR1B1 drives hyperglycemia-induced metabolic reprogramming in MASLD-associated hepatocellular carcinoma.PMC10820337Jain SJorvekar SBBorkar RMSyamprasad NPVaidya JRChalla VSRajdev BKumar GJPanda SRShaik KMShantanu PATripathi DMNaidu VGMfalseAKR1B1 drives hyperglycemia-induced metabolic reprogramming in MASLD-associated hepatocellular carcinoma.<h4>Background & aims</h4>The mechanism behind the progressive pathological alteration in metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH)-associated hepatocellular carcinoma (HCC) is poorly understood. In the present study, we investigated the role of the polyol pathway enzyme AKR1B1 in metabolic switching associated with MASLD/MASH and in the progression of HCC.<h4>Methods</h4>AKR1B1 expression was estimated in the tissue and plasma of patients with MASLD/MASH, HCC, and HCC with diabetes mellitus. The role of AKR1B1 in metabolic switching <i>in vitro was</i> assessed through media conditioning, lentiviral transfection, and pharmacological probes. A proteomic and metabolomic approach was applied for the in-depth investigation of metabolic pathways. Pre2024-01-01T00:00:00Z2024 Feb2025-04-04T09:17:33.278Z2025-04-04T09:17:33.278ZS-EPMC108203373828375710.1016/j.jhepr.2023.100974